BACKGROUND AND
OBJECTIVES: Intraoperative blood transfusions are associated with an increase
in postoperative complications and hospital costs. Thus, this study evaluated
the characteristics, complications, and probable risk factors for death in surgical
patients who needed intraoperative blood transfusions.METHODS: This is a prospective study that spanned a one-year period,
undertaken at the surgical suite of a tertiary hospital. Patients older than
18 years who needed intraoperative blood transfusions were included in this
study. Jehovah witnesses, patients with a history of prior blood transfusions,
coronary failure, and acute brain lesions were excluded.RESULTS: Eighty patients with mean age of 68.4 ± 14.1 years participated
in the study. Most patients were ASA II, representing 69.6% of the study group;
APACHE and POSSUM scores were 13.6 ± 4.4 and 37.5 ± 11.4, respectively.
Mean hemoglobin at the time of transfusion was 8.2 ±1.8 g.dL-1
and 19% of the patients had hemoglobin levels higher than 10 g.dL-1.
Patients received an average of 2.2 ± 0.9 IU of packed red blood cells.
Hospital mortality was 26.3%. Post-transfusion complications totaled 57.5% of
the cases in the postoperative period, and most of them were due to infections.
In the logistic regression, independent factors for death included APACHE II
(OR = 1.34; 95% CI 1.102-1.622), POSSUM (OR = 1.08; 95% CI 1.008-1.150) and
the number of packed red blood cells received (OR = 2.22; 95% CI 1.100-4.463).
Thus, the higher the number of transfusions, the greater the incidence of complications
and mortality.CONCLUSIONS: Hemoglobin level, and the number of packed red blood cells
used were elevated when compared with studies that suggest restrictive strategies.
This sample presented a high incidence of complications, especially infections,
and complications. APACHE II and POSSUM scores and the number of transfusions
were independent risk factors for a worse postoperative prognosis.

In the United States,
in 1986, almost 12.2 million units of red blood packed cells were transfused,
and currently more than 14 million units of blood are administered each year,
two thirds of which are administered in the perioperative period1,2.
Thus, considerable evidence suggests that blood transfusions increase the risk
of complications and death3,4, especially in surgical patients5,6.

Blood transfusion
has a fundamental role in the treatment of severe anemia in surgical patients.
Anemia can lead to an increase in morbidity and mortality associated with generalized
tissue hypoxia. On the other hand, the treatment with blood transfusion is not
devoid of adverse effects.

Patients who received
blood transfusions have the higher mortality rate in the intensive care unit
(ICU) and during hospitalization, greater incidence of multiple organ failure,
and increased length of stay in the ICU7,8. Besides, blood transfusions
are associated with nosocomial infections and this association is directly related
to the number of units transfused (the higher the number of units transfused,
the higher the incidence of nosocomial infections) 9.

Herbert et al.
undertook a large, randomized, multi-center study in an attempt to define the
best treatment strategy of anemia in patients with severe disorders that would
bring about more benefits and less risks. The authors demonstrated that a restrictive
transfusion strategy (transfusion with hemoglobin levels below 7.0 g.dL-1)
is probably more effective than a liberal strategy (transfusions with hemoglobin
levels below 10.0 g.dL-1). Based on those results, currently blood
transfusions are recommended to treat anemia when serum hemoglobin concentrations
are below 7.0 g.dL-1 to maintain hemoglobin levels between 7.0 and
9.0 g.dL-1 10.

Recent data have
demonstrated that the changes in the policy of blood transfusion are subtle.
Some studies demonstrated that mean hemoglobin levels of 8.4 g.dL-1
were a trigger for blood transfusions, and 30% of them were done with hemoglobin
levels above 9.0 g.dL-1.

However, there
are very few prospective clinical studies with surgical patients that evaluate
the real need of intraoperative blood transfusions. In this context, the practical
evaluation of blood transfusions in surgical patients is relevant, besides considering
possible complications associated with this procedure, which is so common in
modern medical practice.

Thus, the objective
of this study was to evaluate the current practice of blood transfusions, verifying
its characteristics, associated complications, and risk factors of death in
surgical patients who need intraoperative blood transfusions.

METHODS

After approval
by the Ethics Commission of the hospital, this study was conducted in the operating
room of a tertiary hospital.

Consecutive patients
undergoing surgeries who needed intraoperative blood transfusions from November
1st, 2006 to November 1st, 2007 participated in this study.

All patients were
18 years or older. Jehovah witnesses, patients with acute cerebral ischemia
or intracranial hypertension, undergoing cardiac surgeries or with acute coronary
insufficiency, with a history of recent blood transfusion (less than 2 weeks),
and those who refused to participate were not included in this study.

To standardize
the data, the worst physiological and laboratorial levels 24 hours before the
surgery were used to determine APACHE II12, SOFA13, MODS14,
and POSSUM15 scores. Those indexes were used to determine the severity
of the patients' conditions, as well as the ASA (American Society of Anesthesiologists)
classification16.

APACHE II (Acute
Physiology and Chronic Health Evaluation) is a two-part score: the physiological
score with 12 parameters, which represents the current compromise of the disease
and assessment of the patient's health condition before admission to the hospital
that indicates pre-morbid conditions. SOFA (Sequential Organ Failure Assessment)
and MODS (Multiple Organ Dysfunction Score) scores added information related
to organ dysfunction, such as cerebral, respiratory, cardiac, hepatic, renal,
and coagulation. The POSSUM (Physiological and Operative Severity Score in the
enUmeration of Mortality and morbidity) score, developed to evaluate the severity
of the conditions of surgical patients, which uses physiological parameters
prior to the surgery, intraoperative parameters, and of the immediate postoperative
period.

Besides, hemoglobin
levels 24 hours before the surgery, immediately before the transfusion, and
after the procedure were considered. The researchers did not have any influence
in the treatment of the patients.

Patients were followed-up
until the end of hospitalization, determining whether they developed organ failure,
such as shock (need of vasoactive drugs for more than one hour), acute renal
failure (ARF), acute respiratory distress syndrome (ARDS), changes in cognition
and behavior, infections, tissue hypoperfusion, the presence of fistulae in
the gastrointestinal tract, and whether the patient was discharged from the
hospital or evolved to death.

The markers of
tissue hypoperfusion used included arterial levels of lactate, base excess,
central venous saturation, urine output, and the difference between the partial
venous and arterial pressure of CO2. Whenever two of those markers
showed changes, the diagnosis of tissue hypoperfusion was made. The levels of
change of the different parameters were: arterial lactate greater than 2 mmol.L-1
17, base excess below -4 mEq/L-1 18, venous oxygen saturation
below 70% 19, urine output below 0.5 mL.kg-1.h-1
20, and a difference between arterial and venous pCO2 greater
than 7 mmHg21.

The data were inserted
in an electronic data bank (Excell - Microsoft) for posterior analysis by a
statistical software (SPSS 13.0).

Initially, the
demographic, clinical, and physiological characteristics of the patients were
described. For the description of the categorical variables, frequencies and
percentages were calculated. Quantitative variables were described as a function
of the central tendency and dispersion.

Patients who received
blood transfusions were divided in survivors (Group 1) and non-survivors (Group
2). The Chi-square test was used for the categorical variables and the Student
t test was used for the continuous variables. Bicaudal statistical tests
were used and the level of significance used was 0.05.

The logistic regression
used through a stepwise analysis was aimed at identifying independent risk factors
and to control the effects of the different confounding variables (mutually
adjusted variables). Variables that showed a probability of significance (p)
less than 0.2 in the univariate analysis among survivors and non-survivors were
considered candidates for the multiple regression analysis. Odds ratio (OR)
and their respective 95% confidence intervals were estimated by logistic regression.

RESULTS

From November 1st,
2006 to November 1st, 2007, 80 patients, 37 males and 43 females,
mean age of 68.4 years, were included in this study. Twenty-one patients were
excluded according to the criteria established. Elective surgeries were more
frequent (81.3%), abdominal surgeries were prevalent with an incidence of 43.8%,
and general anesthesia with neuroaxis blockade were used more often (48.1%)
followed by general combined anesthesia (46.8%) (Table I).

At the time of
the blood transfusion, mean hemoglobin and hematocrit levels were 8.2 ±
1.8 g.dL-1 and 24.3 ± 5.3%, respectively. The incidence of
blood transfusion was higher in patients with pre-transfusion hemoglobin levels
between 8 and 9 g.dL-1 (Table II) (Figure
1).

Postoperative complications
affected 57.5% of the patients, the most frequent occurred up to 28 days after
the blood transfusion, and included infections (36.3%), changes in the markers
of tissue hypoperfusion (30.0%), shock (22.5%), ARF (12.5%), cognitive changes
(11.33%), fistulas of the digestive tract (6.3%), and ARDS (5.0%) (Figure
3).

Therefore, the
number of units of blood transfused was directly proportional to the incidence
of complications and mortality, i.e., the greater the number of units transfused
intraoperatively, the higher the chances of complications and death in the postoperative
period (Figures 4 and 5).

DISCUSSION

Several studies
have demonstrated that the restrictive strategy of blood transfusion is safe
and effective; however, similar to other studies11, this study demonstrated
that the level of hemoglobin that triggered blood transfusion was elevated,
and most patients received transfusions when their hemoglobin levels were between
8 and 9 g.dL-1, and a considerable number of patients who received
blood transfusions with a hemoglobin level greater than 10 g.dL-1.
Besides, a mean of 2.2 units of blood were transfused.

Thus, the high
mortality (26%) observed, despite the number of patients with a low risk of
death, in which most were classified as ASA II and with an APACHE II score around
13, could be related to the decision to transfuse large quantities of blood
in the presence of elevated hemoglobin levels. Besides, it was observed a high
incidence of postoperative complications (57.5%), with a significant incidence
of infections.

Currently, blood
transfusions are considered safe. However, patients continue to develop complications
associated with blood transfusions. The immediate improvement of oxygen delivery
is the expected benefit of this procedure and, therefore, prevents cellular
lesions, but it is difficult to demonstrate those benefits on clinical grounds.

Complications secondary
to blood transfusions can be divided in infectious and non-infectious. Non-infectious
complications include those related with immune modulation that can increase
the inherent risk of infections, as well as acute pulmonary lesions, and other
types of human errors, such as the mistaken identification of the blood type,
which can cause severe hemolytic reactions22.

The pulmonary lesion
related with blood transfusions is one of the most severe complications among
the non-infectious complications. Its incidence is estimated to be approximately
1 to 5,000 transfusions22. The incidence of ARDS in this study was
small, but considerable for the size of the study population, which could be
related to the elevated number of blood transfusions.

Additionally, in
the present study, both pre- and postoperative hemoglobin levels were not capable
of affecting the prognosis of the patients. Therefore, just the hemoglobin level
seems to be insufficient to make a decision to transfuse blood.

Serum hemoglobin
levels are easily obtainable and, in fact, it was used for several years as
a guide to initiate blood transfusions; however, optimal hemoglobin levels vary
considerable among patients, and include several factors, such as age, preexisting
chronic diseases (coronary heart disease), the current diagnosis, and the underline
cause of anemia.

The simple use
of a minimal level of hemoglobin below which every patient should be transfused
and specific levels for specific groups of patients are also inflexible.

Current recommendations
support hemoglobin levels around 7 g.dL-1 as indicative of blood
transfusions23. Besides, studies in human volunteers with isovolumetric
hemodilution demonstrated that hemoglobin levels < 5.0 g.dL-1
did not lead to anaerobic metabolism. Studies in patients who were Jehovah witnesses
demonstrated that survival is possible with even lower levels of hemoglobin.
The case of a patient whose hemoglobin level dropped to 1.8 g.dL-1
and did not demonstrate significant complications, with a good evolution at
the hospital, was reported25; however, extrapolating this result
is very risky to daily medical practice.

The continuous
debate between the risks and benefits of blood transfusions rise doubts regarding
the profile of the patient who really should received packed red blood cells,
and the individual evaluation of each patient and the degree of anemia that
he/she can tolerate are more important.

However, it should
be known how such patients should be evaluated in order to decide whether to
administer packed red blood cells. Thus, clinical exams, along with the data
regarding the diagnosis and comorbidities, can help determine the need of blood
transfusions.

In the population
of the present study, two scores showed a higher degree of importance in the
evaluation of patients, namely APACHE II12 and POSSUM15,
and several studies have demonstrated that they are important prognostic evaluators,
being better than the ASA classification, SOFA or MODS score according to the
logistic regression of the present study, increasing the risk of death with
higher scores. However, those scores involve several clinical and physiological
parameters, decreasing the routine use in the evaluation of surgical patients.
APACHE II scores have been widely used on the admission of patients to the intensive
care unit, and POSSUM scores have been recently validated for use in surgical
patients; thus, it was demonstrated that those scores were important in the
evaluation of the present cohort.

On the other hand,
determining the number of blood units that should be administered seems to be
important in the evolution of surgical patients. A important study4
with intensive care patients demonstrated that the number of transfusions had
a direct correlation with the incidence of infections, which is similar to the
results of the present study, since the higher number of units of blood transfused
increased the incidence of postoperative complications and, consequently, the
mortality, and in this study the risk of death of an additional unit of blood
was 2.2.

The decision to
transfuse and the number of units transfused should be economical and precise.
Patients who need intraoperative blood transfusions, regardless of the type
of surgery, should be carefully evaluated and are patients with increased postoperative
risks. Strategies to prevent the loss of blood26,27 and to increase
the production of red blood cells could also be important in the management
of surgical patients.

Although this study
demonstrated some issues regarding the practice of intraoperative blood transfusions,
one should consider that this was not a multicenter study and the size of the
study population was small, indicating the need of further studies to confirm
our results.

Under the conditions
of the present study, it was possible to conclude that anemia was common in
surgical patients and resulted in several instances of blood transfusions; however,
there is not enough evidence that blood transfusions are beneficial in surgical
patients, according to the observed in this prospective cohort.

Despite the large
number of publications regarding the restrictive strategy of blood transfusions,
higher hemoglobin levels and number of units of blood transfused were observed
in the present study. Elevated APACHE II and POSSUM scores and the higher number
of units of blood transfused were independent risk factors that determined a
worse postoperative prognosis in this population.